Therapy for Relapsed Multiple Myeloma David Dingli, MD, PhD, Sikander Ailawadhi, MD, P. Leif Bergsagel, MD, Francis K. Buadi, MD, Angela Dispenzieri, MD, Rafael Fonseca, MD, Morie A. Gertz, MD, Wilson I. Gonsalves, MD, Susan R. Hayman, MD, Prashant Kapoor, MD, Taxiarchis Kourelis, MD, Shaji K. Kumar, MD, Robert A. Kyle, MD, Martha Q. Lacy, MD, Nelson Leung, MD, Yi Lin, MD, PhD, John A. Lust, MD, PhD, Joseph R. Mikhael, MD, Craig B. Reeder, MD, Vivek Roy, MD, Stephen J. Russell, MD, PhD, Taimur Sher, MD, A. Keith Stewart, MBChB, Rahma Warsame, MD, Stephen R. Zeldenrust, MD, PhD, S. Vincent Rajkumar, MD, Asher A. Chanan Khan, MD  Mayo Clinic Proceedings  Volume 92, Issue 4, Pages 578-598 (April 2017) DOI: 10.1016/j.mayocp.2017.01.003 Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 MSMART risk stratification in relapsed multiple myeloma. ASCT = autologous stem cell transplant; FISH = fluorescence in situ hybridization; GEP = gene expression profiling; MSMART = Mayo Stratification for Myeloma and Risk-Adapted Therapy. Mayo Clinic Proceedings 2017 92, 578-598DOI: (10.1016/j.mayocp.2017.01.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Therapy for multiple myeloma at first relapse. The approach depends on the biology of the relapse (indolent vs aggressive), the performance status of the patient, molecular features of the disease, and the therapeutic history. ASCT = autologous stem cell transplant; DRd = daratumumab, lenalidomide, and dexamethasone; DVd = daratumumab, bortezomib, and dexamethasone; ERd = elotuzumab, lenalidomide, and dexamethasone; ICd = ixazomib, cyclophosphamide, and dexamethasone; IRd = ixazomib, lenalidomide, and dexamethasone; KPd = carfilzomib, pomalidomide, and dexamethasone; KRd = carfilzomib, lenalidomide, and dexamethasone. Mayo Clinic Proceedings 2017 92, 578-598DOI: (10.1016/j.mayocp.2017.01.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Therapy for second or subsequent relapse of multiple myeloma. The decision on which agents to use depends on the therapeutic history and response to previous agents. Triple combination therapy is preferred. ASCT = autologous stem cell transplant; DPCd = daratumumab, pomalidomide, cyclophosphamide, and dexamethasone; DPd = daratumumab, pomalidomide, and dexamethasone; DRd = daratumumab, lenalidomide, and dexamethasone; DVd = daratumumab, bortezomib, and dexamethasone; IMiD = immunomodulatory drug; KPd = carfilzomib, pomalidomide, and dexamethasone; KRd = carfilzomib, lenalidomide, and dexamethasone; PI = proteasome inhibitor. Mayo Clinic Proceedings 2017 92, 578-598DOI: (10.1016/j.mayocp.2017.01.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Patients with quadruple refractory disease have limited treatment options. If eligible, patients should be considered for ASCT. ASCT = autologous stem cell transplant; VDT-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide. Mayo Clinic Proceedings 2017 92, 578-598DOI: (10.1016/j.mayocp.2017.01.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 5 Therapy for secondary plasma cell leukemia or extramedullary multiple myeloma. Fit patients should receive intensive chemotherapy and consolidation by ASCT. Frail patients can be considered for an anthracycline- or daratumumab-based regimen. ASCT = autologous stem cell transplant; CVAD = cyclophosphamide, vincristine, doxorubicin, and dexamethasone; VDT-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide. Mayo Clinic Proceedings 2017 92, 578-598DOI: (10.1016/j.mayocp.2017.01.003) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions